The high-altitude maladaptation syndrome known as chronic mountain sickness (CMS) is characterized by polycythemia and is associated with proteinuria despite unaltered glomerular filtration rate. However, it remains unclear if indigenous highlanders with CMS have altered volume regulatory hormones. We assessed N-terminal pro-B-type natriuretic peptide (NT pro-BNP), plasma aldosterone concentration, plasma renin activity, kidney function (urinary microalbumin, glomerular filtration rate), blood volume, and estimated pulmonary artery systolic pressure (ePASP), in Andean males without (n=14; age=39±11) and with (n=10; age=40±12) CMS at 4330 meters (Cerro de Pasco, Peru). Plasma renin activity (non-CMS: 15.8±7.9 vs. CMS: 8.7±5.4 ng/ml; p=0.025) and plasma aldosterone concentration (non-CMS: 77.5±35.5 vs. CMS: 54.2±28.9 pg/ml; p=0.018) were lower in highlanders with CMS compared to non-CMS, while NT pro-BNP was not different between groups (non-CMS: 1394.9±214.3 vs. CMS: 1451.1±327.8 pg/ml; p=0.15). Highlanders had similar total blood volume (non-CMS: 90±15 vs. CMS: 103±18 ml • kg(-1); p=0.071), but Andeans with CMS had greater total red blood cell volume (non-CMS: 46±10 vs. CMS 66±14 ml • kg(-1); p<0.01) and smaller plasma volume (non-CMS 43±7 vs. CMS 35±5 ml • kg(-1); p=0.03) compared to non-CMS. There were no differences in ePASP between groups (non-CMS 32±9 vs. CMS 31±8 mmHg; p=0.6). A negative correlation was found between plasma renin activity and glomerular filtration rate in both groups (group: r=-0.66; p<0.01; non-CMS: r=-0.60; p=0.022; CMS: r=-0.63; p=0.049). A smaller plasma volume in Andeans with CMS may indicate an additional CMS maladaptation to high-altitude, causing potentially greater polycythemia and clinical symptoms.